A related series of behavioral and electrophysiological experiments are currently underway to further elucidate the neuronal systems and mechanisms underlying the behavioral response to acute and long-term amphetamine treatment. Dose-dependent changes in the firing rate of neurons in the neostriatum, nucleus accumbens, and related neuronal systems (raphe complex and locus coeruleus) are being studied in response to acute systemic injections or central infusions of amphetamine and related compounds. Similar experiments will determine how these drug-induced changes in firing rate are altered by long-term amphetamine treatment. In separate groups of animals, a broad range of antipsychotic drugs are being tested on their ability to reverse amphetamine-induced changes in single unit activity. Apart from these electrophysiological studies, a detailed behavioral analysis of the entire time-course of the amphetamine response will be performed, including a concurrent evaluation of locomotion and focused stereotypy. Attention will be focused on the effects of pharmacological manipulations of dopaminergic, noradrenergic, and serotonergic systems on the multiphasic behavioral response to systemic amphetamine administration. Further evidence for the involvement of these systems in the response to acute and long-term amphetamine treatment will be sought through microinjections of various agents into specific brain sites of freely moving animals.